Crotonyl-aminobenzene-arsonic acids and salts thereof



Patented Apr. 11, 19 33 UNITED STATES PATENT oFFIca E I KARL STREITWOLF, F FRANKFoRT-ON-THE-MAIN, LrRnn senses, en sonniii ON TAUNUs-ANDWALTER HERRMANN, or FRANKFORLON-THE-MAILT, eERMAnY jAssrenoas TO wm'rnnor CHEMICAL COMPANY, mo. or nnwyoax, N."Y A COR-T IPORATION OF NE'W YORK onorom hiirri\ioisnnznriri-aasoi irc ACIDS A sALrs 'rrtnnnon N0 Drawing: Application filed January 39,1930, Serial No. 424,438, and in Germany September 8, 192$ The present invention relates to crotonyl- We have found that by the introduction of the crotonic acid group into 'amino-aryvlarsonic acids compounds are obtained which, compared with other acylamino-arylarsonic acids for instance the acetyl derivatives, show in spite of a reduced"'p oisonousness an increase of the curative power. These acids can be prepared eitherby introducing the crotonylgroup into amino-aryl-arsonic acids,

or by transforming nitro-crotonylamino-aryl H compounds by way of the corresponding amino-crotonylamino -aryls into crotonylamino-aryl arsonic acidslj 1 1 The new arsonic acids yield with'alkalies, ammonia and'organic'bases, such as for instance ethanol amine, saltsfwhich are readi- -ly soluble in waterand, according to the quantity of the base added thereto, the monoe I or di-salts of the acids are obtained. In or-" der to increase the stability of the solutions of these salts preferably small quantities of sodium sulfiteare added thereto.

The new compounds correspond to the following general formula:

The following examples serve to illustrate our invention, but they are not intended to limit it thereto. v

(1) 214 grams of 3-amino-4-hydroxybenzene-arsonic acid are dissolved in 1 liter of normal caustic soda solution. After the soaminobenzene-arsonic acids and salts there lution has been cooled to 0 C; 120 grams of crotonyl chloride and 1200 cc.-,of normal caustic soda solution are simultaneously introduced drop by' drop,the whole is-stirred for a short time and 300 cc. of concentrated hydrochloric acid 'are' then added thereto. a

The i3-'crotonylamino-4-hydroxyb enzeneear sonic acid thusseparated is filtered by Sue tion, washed and dried. It forms a white powder which is easilysoluble in alkalie's.

(2) 620 grams of 3-;aminoe4 hydroxy-5- chlorobenzene-arsonic "acid, obtained reducing the corresponding nitro acid (of. Binc, Bauer, Hallstein, Berichte der' deutschen 1920), page 422), are dissolved! in.2.-9'liters of normal caustic soda solution andthewhole is transformed intogthe ,3-crotonylamino 4e hydroxy-5rchlorobenzene-arsonic acid by 7 means of 35.0 grams of crotonyl'chloride and 3.5.liters of normal caustic sodasolutiom as indicated in Example (1 ).Q Aftergth'eIreactlon --is complete this .acid isseparated by, addition of 870 cc.-of concentrated, hydro 7 chloric' acid. ..;The 3-crotonylam'ino-4-hy- 3 f 'droxyr5-chlorobenzene-arsonicacid isa white crystalline powder, which-is readily; soluble in alkalies. 1 r By causingl99 grams of para amino benzene-a'rsonic acid to react with- 120 grams of crotonylichloride asindicated in Example (1 the para-crotonylaminobenzene-arsonic acidis obtainedin theform-of'a white powder which is easily soluble in ammonia, alkaliesorlorganic bases. i g Other amino-substituted arylarsonic acids can likewise be transformed into their cr0 tonyl derivatives in the same manner.

(4) The salts can be obtained in the following manner: 650 grams of the 3-crotonylamino-4-hydroxyben2ene:l arsonic acid obtained according to Example (1) are made into a paste with water and dissolved by the addition of aboutfg147 I grams of ammonia of 25% strength, The solution is filtered. added to the filtrate (1300 cc.) 1 After addi- V 13 liters of acetone are'gradually tionof "about 4 liters of acetone the salt be} 1 gins-to crystallize out. The ammonium salt 9:

. chemischen .Gresellschaft. 53. i

of the 3 crotonylamino-4-hydroxybenzene-1- arsonic acid is filtered by suction, washed with acetone and ether and dried in a vacuum. The salt crystallizes with 1 mol of 5 crystal water. It forms a ieebly yellowish crystalline powder which is readily soluble I inwater. The aqueous solution of this mono:

, ammonium, salt shows an acid reaction to 4 litmuscpapen. A I c (5) The- 3-crotonylamino l-hydroXy 5- chlorobenzene-arsonio acid obtained accord ing to Example is pasted in the wet state as it comes from the filter with water and dissolved by addition of aqueous a ammonia: of strength; To the filteredsolution is furthermore added a small amount of aqueous ammonla unt1l' blue litmus Paperas well as red litmus paper are changed tored dish with a bluish shade. The solution thus obtained is mixed with 8 liters of c acetone whereby the mono-ammoniumsalt of the acid is separated in a nearly pure white? form.-

It is isolated and" dried as indicatedin Er;- ample (4:).

253 (6) A solution ofthe amino salt prepared according-to Example Qi) can be obtainedbydissolving forlinstance 10 gramsof the salt after additionof 0.125 grams of crystal lized sodium sulfite; adding to the solution aqueous ammonia until blue litmus paper as well as red litmus paper are changed to red dish with a bluish shade and then concentrat ing the-solution as desired. V

Instead of usingthecrystallizedsalts for the preparation of the solution, also the cro-j tonylaminoarylarsonic acids in an aqueous suspension maybe dissolved by addition of equivalent'quantities of'alkali, ammonia or ,iorganic bases, such as for; instance d1ethyl amino-ethanol and the solutions thus obtained which have an amphoterio reaction may be concentrated by addition otwater, preferably after addition of -smallquantities ot crystallized sodium su'lfite.

'are colorless to feebly yellowish. By using instead of 1 mol of the base 2 mols thereof, solutions of the di-salts of the arsenic acids are obtained which have an alkaline reaction.

6O :Wherein one of the Xs stands for the group NH.CO.CH=CH.CH the other Xs for hydrogen chlorineor the hydroxy group and Y for hydrogen, an alkali metal, or NI-L wherein three of the hydrogen atoms may be Isubstituted by two ethyl groups and one hyin acetone or ether andhavi The solutions droxyethyl group being products of them 'peutically valuable properties.

1 2. Compounds of the following formula:

Yxo 1 i A5=b r Y.o

Nnoooneoniom g Y a on wherein -X stands for hydrogen or chlorine and Yforl hydrogen, an alkali metal; or NIL whereinthree of the hydrogen atoms may 5 be substituted by two ethylfgroups and one i hydroxyethyl group being products of therapeutically valuable'properties. i

y 3. Compounds of the following formula 'NHLOW a isl=o c nn.oo.on" on,oni

I a l 90.

wherein Ystands for-hydrogen or the group NIL, being products of therapeutically valuable properties"; i l

' droXy-E-crotonylaniinosbenzene-arsonie acid being a faintly syellowish crystallized powder, easily soluble in wateflnearly insoluble 11g therapeuti cally valuable properties; i r

In testimony whereof, we afiix'our signatures. t 1 l v i KARL STREITVJOLE.

ALFRED FEHRLE. WALTER HEBRMANN.

4.1 The mono am nonium -salt; .Ofa the .eiehy- 

